Comparison of Outcomes of Transfemoral Transcatheter Aortic Valve Implantation Using a Minimally Invasive Versus Conventional Strategy.

Some centers, mostly in Europe, have demonstrated the feasibility of a minimally invasive strategy (MIS; i.e., local anesthesia and conscious sedation, performed in the cath laboratory without transesophageal echocardiography guidance). Nonetheless, the experience of MIS for TAVI using both commercially available valves is lacking in the United States. We, therefore, retrospectively studied all transfemoral TAVI cases performed at our institution between March 2011 and November 2014 to assess the safety and efficacy of MIS. Patients were dichotomized according to the strategy (MIS vs conventional strategy [CS]) used for the procedure. One hundred sixteen patients were included in the MIS group and 91 patients were included in the CS group. Baseline characteristics were similar, and procedural success was comparable (99.1% in MIS and 98.9% in CS, p = 1). One intraprocedural death occurred in each group, whereas conversion rates to general anesthesia were low (3.4%). Comparable device success was obtained. Rates of complications and >mild paravalvular leak before discharge were low and comparable. Length of hospital stay was significantly reduced in the MIS (median, 3.0 [2.0 to 5.0] days) compared with than that in CS group (median 6.0 days [3.5, 8.0]). At a median follow-up of 230 days, no significant difference in survival rate was detected (89% vs 88%, p = 0.9). On average, MIS was associated with remarkable cost saving compared with CS ($16,000/case). In conclusion, TAVI through MIS was associated with a shorter postprocedural hospital stay, lower costs, and similar safety profile while keeping procedural efficacy compared with CS.

Critical role for Syk in responses to vascular injury.

Although current antiplatelet therapies provide potent antithrombotic effects, their efficacy is limited by a heightened risk of bleeding and failure to affect vascular remodeling after injury. New lines of research suggest that thrombosis and hemorrhage may be uncoupled at the interface of pathways controlling thrombosis and inflammation. Here, as one remarkable example, studies using a novel and highly selective pharmacologic inhibitor of the spleen tyrosine kinase Syk [PRT060318; 2-((1R,2S)-2-aminocyclohexylamino)-4-(m-tolylamino)pyrimidine-5-carboxamide] coupled with genetic experiments, demonstrate that Syk inhibition ameliorates both the acute and chronic responses to vascular injury without affecting hemostasis. Specifically, lack of Syk (murine radiation chimeras) attenuated shear-induced thrombus formation ex vivo, and PRT060318 strongly inhibited arterial thrombosis in vivo in multiple animal species while having minimal impact on bleeding. Furthermore, leukocyte-platelet-dependent responses to vascular injury, including inflammatory cell recruitment and neointima formation, were markedly inhibited by PRT060318. Thus, Syk controls acute and long-term responses to arterial vascular injury. The therapeutic potential of Syk may be exemplary of a new class of antiatherothrombotic agents that target the interface between thrombosis and inflammation.

Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results.

BACKGROUND: Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment. METHODS AND RESULTS: An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy. CONCLUSIONS: This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.